Project Summary The overall goal of this research is to determine how the built environment (BE) in which individuals live, work, and play in on a daily basis influences their health. This proposal will continue a productive line of research into associations among the BE and health in a community-based sample of identical twins who were reared together as children but now reside apart as adults. This unique sample permits us to address the serious methodological problems of self-selection and direction of causation because we will examine changes in both the BE and health over time, free of genetic and shared environmental (family) effects that otherwise introduce biases and residual confounding into research of unrelated individuals studied at one point in time. We couple advanced methods in geospatial data analysis and health behavior measurement with integrated spatial databases to obtain measures of physical activity, eating behaviors, and the BE in a real time and space continuum. In this renewal application, we build on our previous work in three important ways. First, we will expand our sample to include greater diversity in ethnicity/race and socio-economic status (SES) because both of these factors profoundly influence residential selection and health. We will also build on our mostly urbanized sample by recruiting twins from less urbanized areas because the BE is very different between these settings, with implications for health. We hypothesize that identical twins who reside in ?healthier? or more ?walkable? BEs have significantly greater walking and moderate-to-vigorous physical activity (MVPA) levels than co-twins who reside in less walkable BEs. We further hypothesize that walking and MVPA levels will differ between identical twin pairs by ethnicity/race, SES, and urban/rural classification. Second, we will establish a cohort of identical twins that will be followed prospectively to address the direction of causation problem. We hypothesize that twin differences in the home neighborhood BE are associated with twin differences in both walking and MVPA levels over time. We further hypothesize that twin differences in the home BE are associated with twin differences in the number of activity and eating events occurring within and outside the home BE over time. Third, we will integrate behavioral with biologic data to investigate epigenetic signatures in obesity-related measures in identical twins, and how these signatures are associated with exposure to an obesogenic BE and health behaviors. We hypothesize that distinct epigenetic signatures (DNA methylation) will be present in obesity- related measures in identical twins, including twins with and without abdominal obesity, and that these signatures will be associated with exposure to an obesogenic BE and activity and eating behaviors. Our scientific approach integrates models from the behavioral and social sciences with molecular and computational measures in a genetically informed twin research design. Ultimately, our unique methods and measures will lead to new and important insights linking epigenetic, environmental, and behavioral aspects of obesity and chronic disease.